DESCRIPTION (Taken from the application): An infectious etiology for reactive arthritis (ReA) has long been suspected since this diseases often follow primary infections of the gastrointestinal, urogenital, and respiratory tracts. While many bacterial species have been associated with the disease, the genital pathogen Chlamydia trachomatis has emerged as a primary agent due to its high prevalence in the population. However, another species of Chlamydia, Chlamydia pneumoniae shows even more widespread prevalence than does C trachomatis. Chlamydia pneumoniae is a pathogen responsible for various respiratory infections and some reports have associated C pneumoniae with heart diseases and even Alzheimer's disease. Importantly, studies from several groups have provided indirect evidence that this organism may be involved in synovial pathogenesis. Preliminary election microscopic (EM) and polymerase chain reaction (PCR) studies of synovia from arthritis patients and asymptomatic patients confirmed the presence of Chlamydia pneumoniae in human synovia. In the present application, we describe studies to confirm and extend our preliminary observations. We will continue our initial screening of the presence of Chlamydia pneumoniae in the synovium of arthritis patients and we will determine whether patients with AD show also synovial Chlamydia pneumoniae with/without joint pathology, at a higher rate than that of standard arthritis patients. The molecular genetic, EM, IH and other laboratory methods required for these studies are already developed or in place in the collaborators' laboratory. The studies proposed in this application will confirm the presence of Chlamydia pneumoniae in the human synovium, and define metabolic characteristics of the organism and host synovial responses to chlamydial infection in addition to th role of APOE in the pathology of C. pneumoniae. Such new information will augment our understanding of the pathogenesis process leading to arthritides.